Evidence b(i)ased medicine—selective reporting from studies sponsored by pharmaceutical industry: review of studies in new drug applications
BMJ 2003; 326 doi: https://doi.org/10.1136/bmj.326.7400.1171 (Published 29 May 2003) Cite this as: BMJ 2003;326:1171
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Melander et al seem to think that their review of data from new drug applications for the serotonin specific reuptake inhibitor (SSRI) class of antidepressants submitted to the Swedish drug regulatory authority is unique.1 In fact, the New Drug Application (NDA) data sets sent to the US Food and Drug Administration (FDA) by the manufacturers of the six most widely prescribed antidepressants have been well analysed.2, 3
Melander et al conclude that recommendation of a specific SSRI is likely to be biased. It is difficult to see from their data why they do not reach the more radical conclusion that their data confirms the lack of evidence for the general effectiveness of antidepressants. From the FDA data, Kirsch et al propose that the small magnitude of the so-called antidepressant effect in clinical trials should be more widely known.3 Melander et al seem to have found a comparable number of half of the clinical trials sponsored by the pharmaceutical companies that failed to find a significant drug/placebo difference. These data reinforce the argument that the small size of the average drug/placebo difference is an artifact associated with the breaking of the blind in clinical trials and of questionable clinical significance.4 Melander et al also helpfully emphasise the potential bias introduced by exclusions after randomisation.5 They note that publications from studies sponsored by the pharmaceutical companies tend to ignore the results of intention to treat analyses and report the more favourable per protocol analyses only.
This issue of bias in clinical trials of antidepressants is to be debated in a motion that antidepressants are no better than placebos at the Critical Psychiatry Network Annual Conference on 13 June 2003 (details at www.criticalpsychiatry.co.uk/AnnualConference2003.htm). The debate is open to the public, as is the whole day conference.
- Melander H, Ahlqvist-Rastad J, Meijer G, Beermann B. Evidence b(i)ased medicine—selective reporting from studies sponsored by pharmaceutical industry: review of studies in new applications. BMJ 2003;326: 1171-3 (31 May) [Abstract/Free Full Text]
- Khan A., Warner HA, & Brown WA Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials: An analysis of the Food and Drug Administration database. Archives of General Psychiatry 2000;57: 311-317
- Kirsch I., Moore TJ, Scoboria A and Nicholls SS. The emperor's new drugs: An analysis of antidepressant medication data submitted to the FDA. Prevention and Treatment, 2000; 5: Article 23, posted July 15, 2002 [Full text]
- Kirsch I & Sapirstein G. Listening to Prozac but Hearing Placebo: A Meta-Analysis of Antidepressant Medication. Prevention & Treatment, 1, Article 0002a, posted June 26, 1998 [Full text]
- Fergusson D, Aaron SD, Guyatt G & Hébert P Post-randomisation exclusions: the intention to treat principle and excluding patients from analysis. BMJ 2002; 325: 652-4 [Full text]
Competing interests:
Founding member of Critical Psychiatry Network
Competing interests: No competing interests
Editors,
A 46 year-long clinical experience allows me to state that the authors are
right stating “any attempt to recommend a specific selective serotonin
reuptake inhibitor from the publicly available data only is likely to be
based on biased evidence” (1). As a matter of fact, in the course of
efficacious therapy with selective serotonin reuptake inhibitors, both
neuronal and cerebral evoked potentials, now-a-days assessed at the bed-
side with the aid of Biophysical Semeiotics in reliable way (2, 3; and
HONCode site 233736, http://digilander.libero.it/semeioticabiofisica) ,
ameliorate clearly. In addition, under identical condition, cerebral
microcirculatory functional reserve improves statistically (3, 4).
Unfortunately, pharmaceutical descriptions of drug significant effects
often do not parallels the reality. Finally, no pharmaceutical companies
have published an only critical paper of mine.
God thanks, doctor can utilize EBM as well as SPBM, i.e. "Single Patient
Based Medicine".
1) Melander H., Ahlqvist-Rastad J. et al. Evidence b(i)ased
medicine—selective reporting from studies sponsored by pharmaceutical
industry: review of studies in new drug applications. BMJ 2003;326:1171
-1173 (31 May)
2) Stagnaro S., Percussione Ascoltata degli Attacchi Ischemici Transitori.
Ruolo dei Potenziali Cerebrali Evocati. Min. Med. 76, 1211 (Pub-Med
indexed for Medline) 1985.
3) Stagnaro S., Valutazione percusso-ascoltatoria della microcircolazione
cerebrale globale e regionale. Atti, XII Congr. Naz. Soc. It. di
Microangiologia e Microcircolazione. 13-15 Ottobre, Salerno, e Acta Medit.
145, 163, 1986).
4) Stagnaro-Neri M., Stagnaro S., Diagnosi precoce dell’invecchiamento
cerebrale con la percussione ascoltata. Monitoraggio terapeutico con la
Nicergolina. Ricerca Med. 6, 348,1989
Competing interests:
None declared
Competing interests: No competing interests
Sir. That the best evidence could be biased was always an issue by
both those in medical practice and scientific research. However, what
seems to have been forgotten is: what about the average patient? - an
important participant in the equation towards better management of disease
and promotion of health. The best evidence based medicine approach is not
only selectively biased in its reporting, it has also major biased
constraints for the care of the individual patient.
It is widely accepted that the integration of clinical expertise with
the best available evidence from systematic research is the foundation of
evidence based medicine. Properly designed Randomised Placebo Controlled
Trials evaluated by a meta - analysis is regarded as the best evidence on
which to base treatment. Yet, a timely reminder from Feinstein and
Horwitz's (1) article shows that the best evidence data that is derived
almost exclusively from randomised trials and meta - analyses that do not
include many types of treatments or patients seen in clinical practice.
Also that 'the best evidence results show comparative efficacy of
treatment for an average randomized patient and not for pertinent
subgroups formed by such cogent clinical features as severity of symptoms,
illness, co-morbidity, and other clinical nuances.'
Moreover they report that randomised trial information is seldom
available for issues in aetiology, diagnosis, and prognosis, and for
clinical decisions that depend on pathophysiologic changes, psychosocial
factors and support, personal preferences of patients, and strategies for
giving comfort and reassurance.
Evidence b(i)ased medicine (2) certainly is biased, even more so for
the average patient who does not adhere to the inclusion criteria that
make up the best practice guidelines of best evidence practice.
Therefore, general practitioners need to assess all of the scientific
evidence rather than just be provided with biased evidence that is limited
to that which is deemed best evidence only. General Practitioners are
then in a position to properly assess treatment options and to monitor the
progress of their patients accordingly. Otherwise the community will
continue to perceive general practitioners to be about biased treatment
only and alternative health practitioners to be about health promotion and
disease prevention.(3)
References
1.Feinstein AR, Horwitz RI. Problems in the "evidence" of "evidence-based
medicine". Am J Med. 1997; 103(6):529-35.
2.Hans Melander, Jane Ahlqvist-Rastad, Gertie Meijer, and Björn Beermann
Evidence b(i)ased medicine-selective reporting from studies sponsored by
pharmaceutical industry: review of studies in new drug applications BMJ
2003; 326: 1171-1173.
3.Reilly D. Comments on complementary and alternative medicine in Europe.
J Altern Complement Med. 2001; 7 Suppl 1:S23-31.
Competing interests:
None declared
Competing interests: No competing interests
Re: Evidence b(i)ased medicine—selective reporting from studies sponsored by pharmaceutical industry: review of studies in new drug applications
I'm rather late to the game with this comment 11 years on, but I can't make figure 1 add up.
The results report finding 38 publications that had arisen from the 42 registered studies. In figure 1 there are indeed 42 blue and red circles; however there are 39 yellow squares and green diamonds.
What am I missing here?
Competing interests: No competing interests